This project focuses on DNA repair of sequence-specific damage caused by psoralens linked to antigene oligonucleotides (pso-AGOs) in human skin cells. The long-term goal is to elucidate the structural factors of DNA which govern its repair in general, and transcription-coupled repair in particular. The research will specifically aim l) To demonstrate specific gene suppression in skin cells caused by treatment with pso-AGOs and ultraviolet A light (UVA); 2) To characterize the targeted damage produced by these agents and determine how the subsequent cellular repair varies with specific sequences or sites in a gene; 3) To determine if DNA repair at one site influences repair at another; and 4) To use a system of differentiating keratinocytes to examine further how transcription controls repair. The research will be executed in the fully equipped laboratory of Professor Philip C. Hanawalt who co-discovered excision repair over 30 years ago and whose laboratory continues to do pioneering work in the field of DNA repair. The laboratory group, departmental and university environments consists of ample and outstanding intellectual and technical support. The research experience will allow the candidate to learn concepts and skills crucial to becoming an independent biomedical scientist. The award will thus serve as preparation to assume a junior faculty position in academic dermatology and to lead a competitive research effort in photobiology and photomedicine related to cutaneous diseases.